1. Field of the Invention
The present invention relates to an implantable medical device, and in particular, to a vascular stent having a continuous coating to encourage the growth of an endothelial cell layer for discouraging restenosis.
2. Brief Description of the Related Art
Narrowing of the arteries (stenosis) may be treated by balloon angioplasty, where a balloon is inflated in the blocked segment of the artery to stretch the artery and flatten the obstruction in order to increase blood flow. Angioplastied arteries may experience a re-narrowing after angioplasty (a process called restenosis). One method of treatment to prevent restenosis is to mechanically hold the artery open with a stent.
A stent is typically an open mesh cylindrical device which fits into the opened artery and expands radially against the walls of the artery. There are two types of stents: 1) balloon expandable stents made of stainless steel mesh and 2) self-expanding (temperature sensitive) stents with a high elasticity, composed of “smart metals”. While most stents are made of type 316 Stainless Steel (SS), there is a recent trend towards using stents made of shape memory alloys containing nickel and titanium (Nitinol). Shape Memory Alloys (SMAs) refer to alloys that retain their original shape when exposed to a certain temperature threshold. These stents are designed to contract or contort under a cold environment and expand or return to their original shape under warm temperatures.
Stents using SMAs contain 55% nickel and 45% titanium and expand automatically at the body temperature of 37° C. to apply a constant radial pressure against the arterial wall, preventing its collapse. Unlike stainless steel stents, which require angioplastic balloon pressure to expand, nitinol stents expand independently. However, nickel is toxic and leaches out over a prolonged period of time. Therefore, nitinol stents require a suitable coating.
While a stent may be effective in preventing restenosis, restenosis can nevertheless occur. Various factors may contribute to restenosis. For example, the stented site may reocclude due to intense coagulation reaction at the stented site. The proliferation of vascular smooth muscle cells over and through the stent may contribute to restenosis.
Current stent research is focused on creating biocompatible stents that remain effective for a long period of time without requiring a second stenting procedure within the affected lumen. Most research focuses on coating the stents with antithrombogenic drugs to prevent platelet aggregation. This approach only shows promise for the short-term delay of restenosis. As the drugs undergo dissolution within the bloodstream, their effectiveness is reduced.
One solution that is occasionally implemented is to insert beta-particle-emitting radioactive drugs or chemicals into the stent to prevent restenosis from occurring. Such a solution is a compromise between the possibility of cancer caused by radiation and the possibility of restenosis caused by a local vascular tissue reaction.
The following describes various attempts that have been made to develop stents that are coated with substances that discourage restenosis.
For example, U.S. Pat. No. 6,231,600 to Zhong discloses a stent with a multilayer coating. In particular, a first layer of polymer such as a polyurethane, including restenosis-inhibiting substances such as paclitaxel, is coupled by a crosslinking agent to a second non-thrombogenic layer. The crosslinking agent is preferably a polyfunctional aziridine and the second layer includes heparin.
U.S. Pat. No. 6,206,914 to Soykan et al. discloses a stent carrying eukaryotic cells, including genetically-engineered endothelial cells, capable of producing and releasing a therapeutic agent. Furthermore, the stent includes a polymer coating covering at least a portion of either the exposed or the wall-contacting surface of the stent. The polymer film may also incorporate anti-thrombogenic or anti-inflammatory agents.
Published U.S. patent application No. 2002/0049495 discloses a stent coated with a polymer such as polyurethane or polyethylene glycol. The polymer incorporates antibodies which promote endothelial cell growth. The endothelial cells may be added to the coated stent before implantation or may grow onto the stent after implantation. The endothelial cells may be genetically modified. The antibodies may be tethered to the polymer layer by linking molecules.
Published U.S. patent application No. 2002/0102560 and U.S. Pat. No. 5,957,972 both disclose genetically modified endothelial cells that may be used to coat stents to prevent restenosis.
Various drugs and cell factors have been suggested to treat restenosis. For example, U.S. Pat. No. 5,516,781 is directed to the treatment of restenosis with rapamycin. U.S. Pat. No. 6,231,600 discloses a stent with a hybrid coating incorporating paclitaxel.
A stent coating must be resistant to 1) bacterial infection, 2) cellular inflammation, 3) a foreign body reaction, 4) platelet aggregation, and 5) corrosion. Polymer coating of implants for improving biocompatibility has a proven efficacy. Some of the polymers used are polyurethane, polylactic acid, and polytetrafluroethylene (PTFE), which is known as Teflon®. The objective of polymer coating is to minimize the foreign-body reaction, which is an inflammatory response characterized by multinucleated giant cells engulfing the stents, platelet formation, and thrombogenesis. Previous studies have shown that polyurethane is one of the most biocompatible polymers; it is flexible, it can be formulated as a hydrophilic coating, and it is not cytotoxic. One type of polyurethane contains aromatic isocyanates. One of the most commonly used polyurethanes for coating is bis(4isocyanatophenyl) methane, also referred to as MDI. Previous studies have shown that hydrophilic polyurethane coatings of implants are one of the most useful and effective biocompatible coatings. Other known biocompatible polymers include polyester and the natural organic polymer, rubber.